Psoriasis

10
Psoriasis


Uwe Wollina


Department of Dermatology and Allergology, Academic Teaching Hospital Dresden, Dresden, Germany


Introduction


Psoriasis (old Greek: ψωρίασις) is a papulosquamous, chronic, or chronic relapsing inflammatory neutrophilic skin disease with significant involvement of T‐lymphocytes, dendritic cells, granulocytes, and epidermal keratinocytes [1].


While the role of innate immunity and T‐lymphocyte activation has been studied extensively in recent decades, the potential role of adipose tissue for inflammation and comorbidities was largely ignored [2, 3].


Incidence and prevalence rates for psoriasis vary depending on genetic background and age (Tables 10.1 and 10.2) [410]. In a recent meta‐analysis, prevalence of psoriasis in adults ranged from 0.51% to 11.43%, and in children from 0% to 1.37% [11].


Table 10.1 Incidence rates for psoriasis.




































Country Incidence (per 100 000 population) Reference
Denmark 199.5 Egeberg et al. 2017
Italy 230.0 Vena et al. 2010
Netherlands 120.0 Donker et al. 1998
South Korea 212.6 Oh et al. 2017
Trinidad and Tobago 1020.0 Suite 2006
UK 129.0 Springate et al. 2016
USA 78.9 Icen et al. 2009

Table 10.2 Psoriasis – medical treatments.






































































Treatment category Examples Level of evidence and remarks
Topical treatments Corticosteroids
Betamethasone
Mometasone
Clobetasol‐17‐propionate
Ia, potent and very potent steroids, less irritating than vitamin D, potential skin atrophy is a controversial issue
Vitamin D derivatives
Calcipotriol
Calcitriol
Tacalcitrol
Ia, irritation, hyperpigmentation, tacalcitrol is the less potent substance, decreased activity in combination with salicylic acid or phototherapy
Dithranol II, most potent topical treatment, irritating, staining, needs some experience
Coal tar IV, better than placebo, staining, smells, photosensitizing, potentially carcinogenic (human scrotal skin only), absolute contraindication: pregnancy, xeroderma pigmentosum, Gorlin‐Goltz syndrome
Retinoids
Tazarotene
II, irritating, burning, pruritus, absolute contraindications are pregnancy and breastfeeding
Fixed combinations
Calcipotriol + betamethasone
Ia, more effective than the single components, for induction therapy
Systemic treatments Phototherapy
UVB‐311 nm
II, erythema, not carcinogenic, time consuming contraindications: gene defects with increases UV‐sensitivity, photoallergic and phototoxic medical drugs
UVB‐308 nm (laser or LED [light‐emitting diodes]) III, erythema, bullae, for small lesions contraindications like UVB‐311 nm
Photochemotherapy (PUVA [psoralen plus ultraviolet A irradiation]) II, most commonly used photosensitizer is 8‐methoxy‐psoralen, erythema, lentigines; oral PUVA has an increased risk for non‐melanoma skin cancer, bath‐ and cream PUVA obviously not contraindications like UVB‐311 nm, oral PUVA: pregnancy, ciclosporin A
Ciclosporin A Ia, fast acting, absolute contraindications: uncontrolled hypertension or renal insufficiency, liver failure, pregnancy, or breastfeeding, pre‐existent malignancies; can cause hypertrichosis and gingival hyperplasia, has numerous drug interactions (greatest relevance in elderly patients)
Fumaric acids II
contraindications: lymphopenia, leukopenia, inflammatory bowel disease, malignancies, renal failure, pregnancy, and breastfeeding; common adverse effects are flushing, gastrointestinal events, and lymphopenia or leukopenia
Methotrexate II
contraindications: liver disease, pregnancy; can induce pneumonitis, cirrhosis (in combination with alcohol or hepatitis), bone marrow depression, peptic ulcers, and skin ulcers
Acitretin II, can be combined with PUVA, absolute contraindications: pregnancy (teratogenic) and breastfeeding, renal and hepatic disorders; can cause dryness of eye, mucous membranes and skin, alopecia, brittle nails
TNF‐alfa inhibitors
Adalimumab
Etanercept
Infliximab
Ia, increased risk of infections, cytopenia, rarely paradoxical psoriasis, lupus‐like syndrome and lymphoma, absolute contraindications: pregnancy and breast‐feeding, severe infections including tuberculosis, chronic heart failure NYHA III or IV (NYHA = New York Heart Association) contraindications: liver failure, malignancies (except basal cell carcinoma), live vaccination
Interleukin (IL) inhibitors
IL‐12/IL‐23p40:
Ustekinumab
Ia, absolute contraindications: pregnancy and breastfeeding, severe infections including tuberculosis, preexistent malignancies (except basal cell carcinoma), live vaccine
IL‐23p19:
Guselkumab,
Risankizumab,
Tildrakizumab
I, fast acting and very effective monoclonal antibodies, trials still ongoing, long term safety has to be evaluated, infections increased
IL‐17A:
Ixekizumab,
Secukinumab
Ia, first line treatments for moderate to severe plaque psoriasis, very effective; adverse effects: increased risk of infections
IL‐17 receptor:
Brodalumab
Ia, very high percentage of PASI 100 response; adverse effects: increased risk of infections including candidiasis, probably increased suicidality
Janus kinase inhibitors:
Tofacitinib
Baricitinib
Not yet approved for psoriasis, increased risk of infections, interstitial pneumonitis
Phosphodiesterase‐4 Inhibitor:
Apremilast
Ia, no need for laboratory monitoring, the common adverse event is diarrhea during treatment initiation

Psoriasis can be subdivided according the age of onset, severity, and morphological appearance. Psoriasis vulgaris, until recently better known as “plaque‐type” psoriasis, is the most common subtype. Psoriasis exanthematica is less common but usually triggered by streptococcal infections. This subtype may show complete remission lasting for many years. Both of these subtypes develop papulosquamous lesions with a silvery desquamation. Pustular psoriasis is characterized by a strong inflammation with significant involvement of neutrophils. The pustules are primarily sterile [12]. The three major pustular psoriasis types include (i) generalized pustular psoriasis (GPP), (ii) acrodermatitis continua of Hallopeau (ACH), and (iii) palmoplantar pustulosis (PPP) [13]. In rare cases, psoriasis can become erythrodermatic involving at least 75% of the body surface. The characteristic clinical symptoms get lost but the severity increases markedly [14].


Psoriasis can affect not only skin but also hair and nails, tendons, entheses, joints, and the uvea. Psoriasis arthritis (PsA) is an entity different in symptomatology and course from rheumatoid arthritis, although it shares features with other sero‐negative spondylarthropathies [12, 15].


Psoriasis, and in particular the more severe and extensive disease, is characterized by important comorbidities. Cardiovascular events contribute to morbidity and mortality among psoriasis patients. It has been assumed that the chronic inflammation is responsible [16]. In addition, metabolic disorders including the metabolic syndrome are associated with a more severe and less treatment‐responsive course. The odds ratio (OR) for metabolic syndrome among psoriasis patients is 2.14 [17].


Genetics of Psoriasis


Psoriasis is a disease not inherited by single gene mutations. Nevertheless, the disease and its subtypes have a genetic background. Five key genes have been identified that increase the risk of psoriasis: PPARD, GATA3, TIMP3, WNT5A, and PTTG1 [18]. Through genome‐wide gene analysis, 16 marker genes were found. FASLG encoding Fas ligand, IKBKE encoding IKK‐ɛ, CHUK encoding IKK‐α, IL31 encoding the cytokine IL‐31, KLRK1 encoding NKG2D, a killer cell lectin‐like receptor, and PTPN2 encoding T cell protein tyrosine phosphatase are involved in activation or regulation of T‐lymphocytes [19].


In a cross‐phenotype mapping of major histocompatibility complex (MHC), the HLA‐C*06:02 allele was protective of PsA compared to psoriasis without joint involvement (Odds ratio [OR] 0.37). No association of PsA to HLA‐C*06:02 was observed. The most significant association of PsA was to amino acid at position 97 of HLA‐B where the presence of asparagine or serine residue increased PsA risk. Asparagine at position 97 of HLA‐B defines the HLA‐B*27 alleles [20].


Pustular psoriasis has a different genetic background with ethnic variations. Loss of function mutations have been detected in IL‐36RN gene encoding the IL‐36 antagonist in palmoplantar and GPP patients from Japan but not in Europe [21, 22].


Epigenetics in Psoriasis – The Importance of Environmental Factors


The interplay between genetic factors and environmental factors is crucial in psoriasis pathogenesis. In contrast to other chronic inflammatory disorders, detailed information about epigenetics in psoriasis is lacking [23].


Deoxyribonucleic acid (DNA) methylation can affect the binding of transcription factors on gene regulatory elements and thereby gene activity and regulation. By epigenome‐wide association analysis, nine most significant loci were identified in psoriatic skin: cg20335425 (5′‐untranslated regions of S100A8), cg13375463 (AHDC1), cg24216770 (DLGAP4), cg13086983 (ECE1), cg19430423 (CYP2S1), cg26756782 (SPIRE2), cg09468264 (intergenic), cg22724943 (MAN1C1), and cg00288598 (EIF2C2) [24].


Hypoacetylation of histone H4 was observed in peripheral blood mononuclear cells of psoriatic patients. The degree of hypoacetylation of H4 was inversely correlated to the psoriasis area and severity index (PASI) score [25].


Micro‐ribonucleic acids (mRNAs) exert immune modulatory effects on various cell types. In psoriasis, miR‐146a is of particular interest since it has been shown to inhibit inflammatory responses in human keratinocytes while targeting FERMT1. In lesional psoriatic skin, expression of miR‐146a and miR‐146b (miR‐146a/b) is increased. It is more strongly induced by stimulation of proinflammatory cytokines in keratinocytes and fibroblasts [26]. Genetic deficiency in miR‐146a leads to earlier onset and exacerbated inflammation, with increased expression of IL‐17‐induced keratinocyte‐derived inflammatory mediators, hyperproliferation of epidermal keratinocytes, and stimulated neutrophil infiltration [27].


Because of the association of psoriasis to metabolic and cardiovascular disorders, genome‐wide analysis has been performed to analyze whether psoriasis, metabolic syndrome, and coronary heart disease share susceptibility loci. While the genetic control of psoriasis is widely independent from both comorbidities, metabolic syndrome and coronary heart disease share 10 common loci. It can be concluded that the comorbidities of psoriasis are mainly influenced by environmental factors such as nutrition and not primarily by a genetic disposition [28].


Metabolomics and Microbiome


Metabolomics of psoriasis demonstrate peculiarities. In lesional skin, glutamic acid, choline, valine, glucose, phenylalanine, and myo‐inositol are increased. Urocanic acid and citrulline are reversely correlated to disease activity. In peripheral blood changes in amino acids, leukotrienes and other compounds were noted [29].


The skin and gut microbiome is also altered in psoriasis. Studies demonstrated a trend toward relative abundance of Streptococcus and a decreased number of Propionibacterium in psoriatic skin. In the gut, the ratio of Firmicutes and Bacteroidetes was perturbed, while Actinobacteria was underrepresented in psoriasis patients compared to healthy controls [30].


Health‐Related Quality of Life


Health‐related quality of life (HRQoL) is assessed in several dimensions, i.e. physical, emotional, social, and functional aspects. HRQoL associated with psoriasis is as much impaired as by other major diseases including in cancer, arthritis, hypertension, heart disease, diabetes, and depression [31, 32].


Physical Complaints in Psoriasis


Pain is a common symptom in psoriasis patients not limited to PsA, traditionally considered to be of peripheral nociceptive origin. Pain sensations are also reported in case of scalp psoriasis and nail involvement [33, 34]. In ACH, pain is due to pustulations of the nail bed and a rapid relief can be obtained after punch biopsies form the nail plate [35]. In PsA, the quality of pain and resulting disability is dependent upon involvement of spine, joints, tendons or entheses [15]. Among patients with chronic inflammatory arthritis including PsA, more than 50% report neuropathic pain. Neuropathic pain is not related to inflammation [36]. This aspect may explain the almost immediate improvement of pain in PsA by intravenous TNF‐alfa inhibitor infliximab [37].


Pruritus is a common complaint in psoriasis but its quality is different from that of atopic dermatitis. One can only rarely see excoriations due to scratching in psoriasis patients. It has been speculated that in psoriasis, substance P might be a major mediator of pruritus [38]. The highest prevalence of pruritus has been reported in psoriasis patients from Italy (91.6%), in France the prevalence was 35.3%. The intensity of pruritus was the highest in Italy and the lowest in Russia [39]. Nevertheless, itch is one of the symptoms that cause a significant reduction in HRQoL in psoriasis. While antihistamines are of very limited efficacy, systemic treatment with biologics such as anti‐interleukin‐(IL)17 inhibitor ixekizumab, janus kinase inhibitor tofacitinib or phosphodiesterase‐4 inhibitor apremilast rapidly reduce pruritus in moderate to severe psoriasis [33, 40, 41].


Intimacy and Sexual Dysfunction


The dermatologic intimacy scale (DIS) developed by the University of California San Francisco was used for 1676 psoriasis patients, with 1109 patients completing the survey. Patients with moderate to severe disease had a higher DIS score than patients with mild psoriasis. Patients with genital involvement had higher scores compared to patients without involvement [42].


A study of two centers, one in Dallas, Texas, and the other one in Dublin, Ireland, investigated the impact of genital psoriasis on quality of life and sexuality. Genital psoriasis had a detrimental effect on quality of life and sexual health as determined by the Dermatology Life Quality Index (DLQI) (P < 0.0001), the Center for Epidemiological Studies‐Depression Scale (P = 0.01), and the Relationship and Sexuality Scale (P < 0.0001) [43].


In male psoriasis patients, the risk of erectile dysfunction is higher dependent on psoriasis severity, psoriatic arthritis, and age. The association of psoriasis to metabolic syndrome and cardiovascular disease does also contribute [44].


Among females with psoriasis, vulvar discomfort, vulvar pruritus, and burning sensations are frequently reported [45].


Depression and Suicidality


“The psychological burden of skin diseases: a cross‐sectional multicenter study among dermatological outpatients in 13 European countries,” run by the European Society of Dermatology and Psychiatry (ESDaP), is an observational, cross‐sectional multicenter study that recruited adult psoriasis patients from dermatological outpatient clinics in 13 European countries from November 2011 to February 2013. There was no association of severity of depression to educational status. On the other hand, patients with the lowest socioeconomic status had more severe anxiety and depressive symptoms and the highest HRQoL impairment. Suicidal ideation related to psoriasis was recorded in 11.5% of patients with a great variability between the countries. The highest prevalence of suicidal thoughts was found in Turkey (44.4%), and the lowest in France (5.9%) [46].


In one meta‐analysis, patients suffering from psoriasis were more likely to exhibit suicidal behaviors, i.e. attempted and completed suicides, with a pooled OR of 1.26. Severity and younger age were risk factors [47]. The issue is controversial – another meta‐analysis failed to demonstrate an increased risk of patients with psoriasis for suicide, suicide attempt, and suicidality [48].


Social Aspects

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Aug 10, 2020 | Posted by in Dermatology | Comments Off on Psoriasis
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